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Colon-Targeted Adhesive Hydrogel Microsphere for Regulation of Gut Immunity and Flora
Advanced Science ( IF 14.3 ) Pub Date : 2021-07-22 , DOI: 10.1002/advs.202101619 Hua Liu 1 , Zhengwei Cai 2 , Fei Wang 2 , Liwen Hong 1 , Lianfu Deng 2 , Jie Zhong 1 , Zhengting Wang 1 , Wenguo Cui 2
Advanced Science ( IF 14.3 ) Pub Date : 2021-07-22 , DOI: 10.1002/advs.202101619 Hua Liu 1 , Zhengwei Cai 2 , Fei Wang 2 , Liwen Hong 1 , Lianfu Deng 2 , Jie Zhong 1 , Zhengting Wang 1 , Wenguo Cui 2
Affiliation
Intestinal immune homeostasis and microbiome structure play a critical role in the pathogenesis and progress of inflammatory bowel disease (IBD), whereas IBD treatment remains a challenge as the first-line drugs show limited therapeutic efficiency and great side effect. In this study, a colon-targeted adhesive core–shell hydrogel microsphere is designed and fabricated by the ingenious combination of advanced gas-shearing technology and ionic diffusion method, which can congregate on colon tissue regulating the gut immune-microbiota microenvironment in IBD treatment. The degradation experiment indicates the anti-acid and colon-targeted property of the alginate hydrogel shell, and the in vivo imaging shows the mucoadhesive ability of the thiolated-hyaluronic acid hydrogel core of the microsphere, which reduces the systematic exposure and prolongs the local drug dwell time. In addition, both in vitro and in vivo study demonstrate that the microsphere significantly reduces the secretion of pro-inflammatory cytokines, induces specific type 2 macrophage differentiation, and remarkably alleviates colitis in the mice model. Moreover, 16S ribosomal RNA sequencing reveals an optimized gut flora composition, probiotics including Bifidobacterium and Lactobacillus significantly augment, while the detrimental communities are inhibited, which benefits the intestinal homeostasis. This finding provides an ideal clinical candidate for IBD treatment.
中文翻译:
用于调节肠道免疫和菌群的结肠靶向粘附水凝胶微球
肠道免疫稳态和微生物结构在炎症性肠病(IBD)的发病机制和进展中发挥着关键作用,而一线药物治疗效果有限且副作用大,IBD治疗仍然是一个挑战。本研究通过先进的气体剪切技术和离子扩散方法的巧妙结合,设计并制备了一种结肠靶向粘附核壳水凝胶微球,该微球可以聚集在结肠组织上,调节肠道免疫微生物群微环境,从而治疗IBD。降解实验表明了海藻酸盐水凝胶壳的抗酸和结肠靶向特性,体内成像显示了微球硫醇透明质酸水凝胶核的粘膜粘附能力,减少了系统暴露并延长了局部药物的时间停留时间。此外,体外和体内研究均表明,微球显着减少促炎细胞因子的分泌,诱导特异性2型巨噬细胞分化,并显着减轻小鼠模型中的结肠炎。此外,16S核糖体RNA测序揭示了优化的肠道菌群组成,包括双歧杆菌和乳杆菌在内的益生菌显着增加,同时有害群落受到抑制,这有利于肠道稳态。这一发现为 IBD 治疗提供了理想的临床候选药物。
更新日期:2021-09-22
中文翻译:
用于调节肠道免疫和菌群的结肠靶向粘附水凝胶微球
肠道免疫稳态和微生物结构在炎症性肠病(IBD)的发病机制和进展中发挥着关键作用,而一线药物治疗效果有限且副作用大,IBD治疗仍然是一个挑战。本研究通过先进的气体剪切技术和离子扩散方法的巧妙结合,设计并制备了一种结肠靶向粘附核壳水凝胶微球,该微球可以聚集在结肠组织上,调节肠道免疫微生物群微环境,从而治疗IBD。降解实验表明了海藻酸盐水凝胶壳的抗酸和结肠靶向特性,体内成像显示了微球硫醇透明质酸水凝胶核的粘膜粘附能力,减少了系统暴露并延长了局部药物的时间停留时间。此外,体外和体内研究均表明,微球显着减少促炎细胞因子的分泌,诱导特异性2型巨噬细胞分化,并显着减轻小鼠模型中的结肠炎。此外,16S核糖体RNA测序揭示了优化的肠道菌群组成,包括双歧杆菌和乳杆菌在内的益生菌显着增加,同时有害群落受到抑制,这有利于肠道稳态。这一发现为 IBD 治疗提供了理想的临床候选药物。